Abstract Background Shock index (SI) and age shock index (ASI) are less frequently used for assessment of major adverse cardiovascular events (MACE) among patients with ST-segment elevation myocardial infarction (STEMI), and their reported cut-off points are controversial. Objectives We aimed to define proper cut-off value of these indices for MACE prediction among Iranian patients with STEMI. Methods This study was in the context of the ST-Elevation Myocardial Infarction Cohort in Isfahan (SEMI-CI) study. SI and ASI were calculated by division of heart rate (HR) over systolic blood pressure (SBP) and age multiplied by SI, respectively, in 818 subjects with STEMI. Receiver operating characteristic (ROC) curve analysis was used to determine optimal SI and ASI cut-off values. Chi-square test, independent t test, and analysis of variance were employed for nominal and numerical variables, as appropriate, with consideration of p values < 0.05. MACE was defined as a composite of non-fatal reinfarction, heart failure (HF), recurrent percutaneous intervention (PCI), rehospitalization for cardiovascular diseases, and all-cause mortality. Results Mean age was 60.70 ± 12.79 years (males: 81.7%). Area under curve (AUC) values from ROC curve analysis for SI and ASI were 0.613 (95% confidence interval [CI]: 0.569 to 0.657, p < 0.001) and 0.672 (95% CI: 0.629 to 0.715, p < 0.001), respectively. Optimal SI and ASI cut-offs were 0.61 (sensitivity: 61%, specificity: 56%) and 39.5 (sensitivity: 65%, specificity: 66%), respectively. Individuals with SI ≥ 0.61 or within the highest quartile (SI ≥ 0.75) had significantly higher frequency of one-year MACE compared to the reference group (34.7% versus 22.2%, p < 0.001 and 42.4% versus 20.6%, p < 0.05, respectively). Similar relations were observed in terms of ASI values (ASI ≥ 39.5 versus ASI < 39.5: 43.6% versus 17.3%, p < 0.001, ASI Q4 ≥ 47.5 versus ASI Q1 ≤ 28.8: 49% versus 16.6%, p < 0.05). Conclusions SI and ASI cut-off values of 0.61 and 39.5 could reliably predict MACE occurrence among Iranian patients with STEMI. (MACE STsegment ST segment STEMI, STEMI , (STEMI) cutoff cut off controversial STElevation Elevation SEMICI SEMI CI (SEMI-CI HR (HR SBP (SBP respectively 81 (ROC Chisquare Chi square test variables appropriate 005 0 05 0.05 nonfatal non fatal reinfarction HF, HF (HF) PCI, PCI (PCI) diseases allcause all cause mortality 6070 60 70 60.7 1279 12 79 12.7 males (males 81.7%. 817 81.7% . 7 81.7%) AUC (AUC 0613 613 95% 95 (95 [CI] 0569 569 0.56 0657 657 0.657 0001 001 0672 672 0.67 0629 629 0.62 0715 715 0.715 cutoffs offs 061 61 0.6 sensitivity (sensitivity 61% specificity 56% 56 395 39 5 39. 65 65% 66%, 66 66% 66%) 0.75 075 75 oneyear one year 34.7% 347 34 (34.7 222 22 2 22.2% 0.00 424 42 4 42.4 206 20 6 20.6% respectively) 436 43 43.6 173 17 3 17.3% Q 475 47 47. 28.8 288 28 8 49 166 16 16.6% 0.05) (STEMI 00 0.0 (HF (PCI 607 60. 127 1 12. 81.7 9 (9 [CI 056 0.5 065 0.65 000 067 67 062 62 071 71 0.71 06 0. 0.7 07 34.7 (34. 22.2 42. 20.6 43. 17.3 28. 16.6 81. ( 34. (34 22. 20. 17. 16. (3